Fluoride supplements and fluorosis: a meta-analysis.
This paper presents a systematic review of the dental literature that was carried out to investigate whether the regular use of fluoride supplements in non-fluoridated communities during the period of tooth development increases the risk of dental fluorosis. A MEDLINE search was organized for all documents published, in English, between January 1966 and September 1997 using the following key words: fluorosis, dental, fluoride, fluoride supplement or supplements, drop or drops, and tablet or tablets. Twenty-four studies that assessed the development of dental fluorosis in children who had used fluoride supplements earlier in their life were included in this review. Of the 24 studies, 10 were cross-sectional/case control studies and four were follow-up studies. These studies had data that allowed a quantitative estimation of the risk of developing dental fluorosis in users of fluoride supplements. The other 10 studies were excluded because they either did not present enough data or had other methodological problems. A qualitative review of the studies found a consistent and strong association between the use of fluoride supplements and dental fluorosis. The meta-analyses of the cross-sectional/case-control studies estimated that the odds ratio of dental fluorosis in users of fluoride supplements compared with non-users ranged between 2.4 and 2.6. The meta-analyses of the follow-up studies estimated that the relative risk in long-term users was between 5.5 and 12.2. This review confirmed that in non-fluoridated communities the use of fluoride supplements during the first 6 years of life is associated with a significant increase in the risk of developing dental fluorosis.


Genuinely Ferroelectric Sub-1-Volt-Switchable Nanodomains in Hf xZr(1- x)O2 Ultrathin Capacitors.
The new class of fully silicon-compatible hafnia-based ferroelectrics with high switchable polarization and good endurance and thickness scalability shows a strong promise for new generations of logic and memory devices. Among other factors, their competitiveness depends on the power efficiency that requires reliable low-voltage operation. Here, we show genuine ferroelectric switching in Hf xZr(1- x)O2 (HZO) layers in the application-relevant capacitor geometry, for driving signals as low as 800 mV and coercive voltage below 500 mV. Enhanced piezoresponse force microscopy with sub-picometer sensitivity allowed for probing individual polarization domains under the top electrode and performing a detailed analysis of hysteretic switching. The authentic local piezoelectric loops and domain wall movement under bias attest to the true ferroelectric nature of the detected nanodomains. The systematic analysis of local piezoresponse loop arrays reveals a totally unexpected thickness dependence of the coercive fields in HZO capacitors. The thickness decrease from 10 to 7 nm is associated with a remarkably strong decrease of the coercive field, with about 50% of the capacitor area switched at coercive voltages ≤0.5 V. Our explanation consistent with the experimental data involves a change of mechanism of nuclei-assisted switching when the thickness decreases below 10 nm. The practical implication of this effect is a robust ferroelectric switching under the millivolt-range driving signal, which is not expected for the standard coercive voltage scaling law. These results demonstrate a strong potential for further aggressive thickness reduction of HZO layers for low-power electronics.


Marine drugs from sponge-microbe association--a review.
The subject of this review is the biodiversity of marine sponges and associated microbes which have been reported to produce therapeutically important compounds, along with the contextual information on their geographic distribution. Class Demospongiae and the orders Halichondrida, Poecilosclerida and Dictyoceratida are the richest sources of these compounds. Among the microbial associates, members of the bacterial phylum Actinobacteria and fungal division Ascomycota have been identified to be the dominant producers of therapeutics. Though the number of bacterial associates outnumber the fungal associates, the documented potential of fungi to produce clinically active compounds is currently more important than that of bacteria. Interestingly, production of a few identical compounds by entirely different host-microbial associations has been detected in both terrestrial and marine environments. In the Demospongiae, microbial association is highly specific and so to the production of compounds. Besides, persistent production of bioactive compounds has also been encountered in highly specific host-symbiont associations. Though spatial and temporal variations are known to have a marked effect on the quality and quantity of bioactive compounds, only a few studies have covered these dimensions. The need to augment production of these compounds through tissue culture and mariculture has also been stressed. The reviewed database of these compounds is available at www.niobioinformatics.in/drug.php.


Evaluation of efficacy and safety of an inactivated virus vaccine against feline leukemia virus infection.
An inactivated virus vaccine was developed for prevention of FeLV infection in domestic cats. When given in 2 doses, 3 weeks apart, to cats that were greater than or equal to 9 weeks old at the time of first vaccination, the vaccine prevented persistent viremia from developing in 132 of 144 (92%) vaccinates after oronasal challenge exposure with virulent FeLV. In contrast, persistent viremia developed after oronasal challenge exposure with FeLV in 39 of 45 (87%) age-matched nonvaccinated control cats. Transient viremia, indicated by early detection of p27 by ELISA in serum of cats protected from persistent viremia at 12 weeks after challenge exposure, was found in 10 of 132 (8%) vaccinates. Cats that were aviremic 12 to 16 weeks after challenge exposure were examined for reactivation of latent FeLV infection; 4 weekly doses of methylprednisolone were administered, followed by in vitro culture of bone marrow cells. Latent infection was readily reactivated in 6 of 8 (75%) nonvaccinated control cats that had been transiently viremic after challenge exposure. However, latent infection was reactivated in only 5 of 48 (10%) protected vaccinates, and in none of 38 vaccinates in which transient viremia had not been detected. In a safety field trial, only 34 mild reactions of short duration were observed after administration of 2,379 doses of vaccine to cats of various ages, breeds, and vaccination history, for a 1.43% reaction rate. Results indicate that the aforementioned inactivated virus vaccine is safe and efficacious for the prevention of infection with FeLV.


Sexuality for patients with gynecologic cancer.
Many women who experience gynecologic cancer have significant sexual problems. Many of these women are currently surviving for a longer time and need to experience the best quality of life possible, including their sexual life. Sexual rehabilitation therefore must be an integral part of their treatment. This article provides a knowledge base for nurses about gynecologic site-specific concerns, including assessment techniques and interventions.


Surgical prophylaxis in practice.
The use of antibacterial prophylaxis of postoperative infections is firmly established within clean-contaminated procedures. For clean procedures, prophylaxis has traditionally been reserved for operations involving foreign-body implantation. However, evidence that postoperative infections from non-prosthetic clean procedures are highly under-reported suggests that prophylaxis is also advisable, at least for some non-prosthetic procedures, such as breast surgery and herniorrhaphy. Although cefazolin is recommended by current guidelines, cefuroxime and cefamandole have a broader antimicrobial spectrum and should be preferred in clean prosthetic surgery prophylaxis. In this type of surgery glycopeptides are not recommended for routine use but may have a role for major prosthetic implantation in units with a high incidence of methicillin-resistant staphylococci. In the case of clean-contaminated procedures, cefazolin is recommended for routine use, although colorectal procedures require an agent with improved anti-anaerobic activity. In addition, experience has shown that obstetric/gynaecological, gastroduodenal and biliary tract surgery and appendectomy all require broad-spectrum antibacterial prophylaxis. Suitable agents include cefoxitin, cefotetan, ureidopenicillins and beta-lactam/beta-lactamase inhibitor combinations. The traditional surgical classification scheme needs to be replaced with a classification that additionally accounts for patient-specific risk factors. The limitations of the current scheme may partly explain why current guidelines are so seldom followed in clinical practice.


Joint cardiac and respiratory motion estimation for motion-corrected cardiac PET-MR.
Respiratory and cardiac motion can strongly impair cardiac PET image quality and tracer uptake quantification. Standard gating techniques can minimize these motion artefacts but suffer from low signal-to-noise ratio because only a small percentage of the total data is utilized. Motion correction approaches have been proposed to overcome this problem but require accurate knowledge of such physiological motion. Here we present a joint PET-MR motion estimation approach which combines complimentary dynamic image information from simultaneously acquired MR and PET to ensure improved cardiac and respiratory motion estimation for motion-corrected image reconstruction (MCIR) of PET images. A 3D triple-echo Dixon MR scan is used both for calculation of MR-based attenuation correction (AC) maps and estimation of physiological motion. PET listmode data is obtained simultaneously to the MR acquisition which is used for a joint motion estimation and reconstruction of the final MCIR PET. In a first step, dynamic cardiac and respiratory motion resolved 4D MR and PET images are reconstructed. These image series are used in a joint image registration to estimate non-rigid cardiac and respiratory motion fields. In a second step, the motion fields are utilized in a MR MCIR to obtain cardiac and respiratory resolved dynamic MR-based AC maps. In the last step, the non-rigid motion fields and the dynamic AC maps are applied in a PET MCIR to obtain the final motion-corrected PET images. PET-MR data has been obtained in six patients without any known heart disease. Motion amplitudes were between 5.6 and 16 mm, with higher values in the basal compared to the mid-ventricular and apical segments. The proposed joint PET-MR motion estimation provided more accurate motion estimation than using either modality separately. The underestimation of PET uptake due to respiratory and cardiac motion artefacts in the AC maps was up to 17%. The average increase in uptake values using MCIR was 23% ± 10% (p < 0.0001), with values of 28% ± 11% (p < 0.0001) for basal, 21% ± 8% (p < 0.0001) for mid-cavity and 17% ± 7% (p < 0.0001) for apical segments. With the proposed scheme we could ensure high PET image quality and improve local PET uptake quantification by up to 30%. Attenuation correction and motion information was obtained from the same PET-MR raw data, which was obtained during free-breathing to minimize scan times and to increase patient comfort.


Creating ribosomes with an all-RNA 30S subunit P site.
Ribosome crystal structures have revealed that two small subunit proteins, S9 and S13, have C-terminal tails, which, together with several features of 16S rRNA, contact the anticodon stem-loop of P-site tRNA. To test the functional importance of these protein tails, we created genomic deletions of the C-terminal regions of S9 and S13. All of the tail deletions, including double mutants containing deletions in both S9 and S13, were viable, showing that Escherichia coli cells can synthesize all of their proteins by using ribosomes that contain 30S P sites composed only of RNA. However, these mutants have slower growth rates, indicating that the tails may play a supporting functional role in translation. In vitro analysis shows that 30S subunits purified from the S13 deletion mutants have a generally decreased affinity for tRNA, whereas deletion of the S9 tail selectively affects the binding of tRNAs whose anticodon stem sequences are most divergent from that of initiator tRNA.


Toward Precision Psychiatry in Bipolar Disorder: Staging 2.0.
Personalized treatment is defined as choosing the "right treatment for the right person at the right time." Although psychiatry has not yet reached this level of precision, we are on the way thanks to recent technological developments that may aid to detect plausible molecular and genetic markers. At the moment there are some models that are contributing to precision psychiatry through the concept of staging. While staging was initially presented as a way to categorize patients according to clinical presentation, course, and illness severity, current staging models integrate multiple levels of information that can help to define each patient's characteristics, severity, and prognosis in a more precise and individualized way. Moreover, staging might serve as the foundation to create a clinical decision-making algorithm on the basis of the patient's stage. In this review we will summarize the evolution of the bipolar disorder staging model in relation to the new discoveries on the neurobiology of bipolar disorder. Furthermore, we will discuss how the latest and future progress in psychiatry might transform current staging models into precision staging models.


Stimulation of corticotrophin-releasing hormone release by the obese (ob) gene product, leptin, from hypothalamic explants.
Recent data have suggested that adipocytes synthesize and secrete a 16 kDa peptide which acts centrally to regulate weight gain by suppressing appetite and activating the sympathetic nervous system. To exert such effects, it may function as an endogenous ligand in the CNS, since specific receptors (OB-R) have been recently reported to be widely distributed in the brain. We have speculated that this peptide, now known as leptin, may act centrally by stimulating the release of corticotrophin-releasing hormone (CRH), a recognized potent inhibitory modulator of appetite. We tested in vitro the effect of murine leptin on CRH secretion in the dose range of 0.1 pM-100 nM. The static rat hypothalamic incubation system used involved fresh hypothalamic explants maintained in EBSS with consecutive 20 min incubations, and estimation of CRH concentrations in the medium by a specific and sensitive radioimmunoassay. The effect of heat-denatured leptin at a dose of 1 nM and 10 nM, was also investigated. Any possible modulation of leptin effects by adrenergic pathways was then explored by coincubating hypothalami with leptin 10 nM and equimolar concentrations of the alpha 1-adrenergic antagonist prazosin or the beta-adrenergic antagonist propranolol. The active leptin, but not the heat-inactivated peptide, caused a dose-dependent stimulation of CRH release in vitro (p < 0.05- < 0.0001 vs control), with a plateau effect at a dose of 10 nM. The addition of either prazosin or propranolol was without effect on leptin-dependent CRH stimulation. These findings are consistent with the reported presence of leptin receptors in the rat brain, and suggest that leptin may act to regulate appetite at least in part by directly modulating the secretion of CRH from the hypothalamus. It would also appear that such effect occurs via a non-adrenergic mechanism.


In vivo quantitation of regional cerebral blood flow in glioma and cerebral infarction: validation of the HIPDm-SPECT method.
Iodine-123 labeled hydroxyiodopropyldiamine (HIPDm) is a diffusible indicator with an 85%-90% extraction fraction and stable retention in the brain for more than 2 hr. Equilibrium-phase imaging and quantitation using single-photon emission computed tomographic (SPECT) scanning defined a distribution of HIPDm in proportion to regional cerebral blood flow (rCBF). Studies in calves affirmed a close correspondence (r = 0.97) in calculated rCBF between HIPDm and microspheres using the tissue deposition-arterial input function microsphere methodology. Using this same mathematical analysis in vivo, reproducible rCBF data within the expected range of normal were obtained on repeated studies in the same nonhuman primate. With a diffuse encephalopathy secondary to subarachnoid blood, a bilaterally symmetric decrease in rCBF was present. A prominent focal decrease in HIPDm accumulation and calculated rCBF was noted with cerebral infarction in the distribution of a ligated middle cerebral artery. Patient studies with glioma revealed diminished HIPDm accumulation due to decreased flow and/or pH in the region of the neoplasm as well as in the associated vasogenic edema and overlying gray matter.


Patients with deep venous thrombosis and thrombophilia risk factors have a specific prolongation of the lag time in a chromogenic thrombin generation assay.
The objective of the present study was to evaluate the influence of thrombophilia risk factors on variables of a chromogenic thrombin generation assay (ETP) in a setting with acute deep venous thrombosis (DVT) and non-DVT patients. In 152 outpatients suspected for DVT, the results of thrombophilia investigations were known. In all patients, thrombin generation parameters were determined and related to the presence of thrombophilia risk factors. The thrombin generation results were divided in quartiles to calculate the odds ratio, as a measure of the association with thrombophilia risk factors, corrected for age and sex. The groups with and without DVT were analysed independently. From the 152 patients, there were 108 patients with and 44 without DVT. In the DVT-positive group, lag time was significantly prolonged (21.9 versus 20.3 s; P=0.021) in patients with known thrombophilia risk factors (n=48). The odds ratio for thrombophilia risk factors was 3.7 (95% CI 1.1-12) uncorrected and 4.3 (95% CI 1.2-16) corrected for age and sex, both P values less than 0.05. No differences in ETP parameters were observed in patients without DVT with known thrombophilia risk factors (n=32). The relationship of thrombophilia risk factors with the occurrence of a prolonged lag time in the acute phase of DVT is a new finding. Increased coagulation activation may be the consequence of the thrombophilia risk factors with this observation. To unravel whether the test expresses increased consumption or increased release of anticoagulant factors may open new ways to develop diagnostic methods to add to further refinement of exclusion algorithms for DVT.


Geographical distribution of domestic animals: a historical perspective.
Our understanding of the history of animal domestication has been built on regular input from archaeozoology. This fast-expanding discipline uses increasingly sophisticated and specialised tools to enhance our knowledge of phenomena dating back, for the oldest species, to the Neolithic Revolution. This article takes three examples, those of the domestic dog, domestic goat and European rabbit, to illustrate the history of three different domestication processes using the contemporary means available. In each of the three cases, the authors define the location of original domestication, analyse the principal routes of species movements following domestication, discuss the possible reasons for domestication and suggest a few likely epidemiological impacts.


Localization of lectin binding sites in human, cat, and rabbit corneas.
Paraffin sections of human, cat, and rabbit corneas were stained with nine lectins, using an avidin-biotin-complex procedure to study glycoconjugates of the epithelium, keratocytes, and stromal matrix. Wheat germ agglutinin (WGA) stained plasma membranes of all epithelial cell layers of cat and human and superficial and wing cells of rabbit. Plasma membranes of superficial and wing cells of cat epithelium also stained with peanut agglutinin (PNA) and Ricinus communis agglutinin I (RCA-I). Human and cat keratocytes stained with WGA and RCA-I. Stromal matrices of all three species were stained with concanavalin A and lentil agglutinin. In neuraminidase-treated sections, the entire epithelium and keratocytes of all three species stained with PNA. Corneal sections from the three species did not stain with Bandeiraea simplicifolia I, Bandeiraea simplicifolia II, Ulex europeus I, and Soybean agglutinin. These data suggest the presence of oligosaccharides with: N-acetylglucosamine/sialic acid residues in cell membranes of corneal epithelium of all species studied and in the keratocytes of human and cat; terminal beta-galactose residues in cat and human keratocytes, beta-galactose-galactosamine chains in cat epithelial cell membranes; and sialic acid-beta-galactose-galactosamine chains in epithelial cell membranes and keratocytes of all three species.


Morphological Versatility in the Self-Assembly of Val-Ala and Ala-Val Dipeptides.
Since the discovery of dipeptide self-assembly, diphenylalanine (Phe-Phe)-based dipeptides have been widely investigated in a variety of fields. Although various supramolecular Phe-Phe-based structures including tubes, vesicles, fibrils, sheets, necklaces, flakes, ribbons, and wires have been demonstrated by manipulating the external physical or chemical conditions applied, studies of the morphological diversity of dipeptides other than Phe-Phe are still required to understand both how these small molecules respond to external conditions such as the type of solvent and how the peptide sequence affects self-assembly and the corresponding molecular structures. In this work, we investigated the self-assembly of valine-alanine (Val-Ala) and alanine-valine (Ala-Val) dipeptides by varying the solvent medium. It was observed that Val-Ala dipeptide molecules may generate unique self-assembly-based morphologies in response to the solvent medium used. Interestingly, when Ala-Val dipeptides were utilized as a peptide source instead of Val-Ala, we observed distinct differences in the final dipeptide structures. We believe that such manipulation may not only provide us with a better understanding of the fundamentals of the dipeptide self-assembly process but also may enable us to generate novel peptide-based materials for various applications.


Release of endogenous excitatory amino acids in the neostriatum of the rat under physiological and pharmacologically-induced conditions.
There is immunohistochemical evidence suggesting that glutamate (Glu) is released from nerve terminals and acts, via several receptor subtypes, as a major excitatory neurotransmitter in the cortico-striatal pathway of the rat. Aspartate (Asp) is also present in cortico-striatal neurons, but its role as a neurotransmitter has been questioned, since, in contrast to Glu, it has not been demonstrated in presynaptic vesicles. Glu and Asp can be found at submicroM concentrations in the extracellular compartment of most areas of the basal ganglia. Their concentrations are largely regulated by transport mechanisms, but also by a synaptotagmin-dependent exocytotic release, and are sufficiently high to occupy junctional and extrajunctional receptors. We have investigated whether Glu and Asp release in the neostriatum can be selectively modulated by different neuronal systems. Dopamine (DA) and cholecystokinin (CCK) selectively stimulate Asp release, via D1 and CCKB receptor subtypes, respectively. Also opioid kappa-agonists increase Asp release. We propose that the selective modulation of Asp release by D1-, CCKB- and kappa-agonists involves striatal neurons containing Asp, but not Glu. In contrast, local perfusion with the mu-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) increases both Glu and Asp release. This effect is probably exerted on cortico-striatal terminals, via presynaptic inhibitory mu-receptors. Thus, these results demonstrate that extracellular levels of Glu and Asp are modulated differentially by different neuronal systems, and suggest that in the neostriatum of the rat there are neuronal populations using Glu and/or Asp as messenger(s).


[Chronic autoimmune thyroiditis and C-cell hyperplasia. Study of calcitonin secretion in 24 patients].
Serum calcitonin (CT) was determined by radioimmunoassay, using two monoclonal antisera, in 22 women and two men, who had Hashimoto's thyroiditis as confirmed by echographic, immunological or cytological criteria; in 23 patients, serum CT levels were measured after intravenous infusion of pentagastrin (Pg). In 21 cases, basal and Pg stimulated serum CT concentrations were normal. A 61-year-old woman and a 63-year-old man, both euthyroid, had high serum basal CT: 12 pg/ml and 35 pg/ml; infusion of Pg resulted in abnormal increases in serum CT levels: respectively 64 pg/ml and 115 pg/ml. Another patient, a 65-year-old woman with primary hypothyroidism had high serum basal CT: 90 pg/ml (the Pg stimulation test was not done because of ischemic heart disease). Each of these 3 patients had a total thyroidectomy. Pathological examination of the thyroid showed typical features of Hashimoto's thyroiditis and extensive C-cell hyperplasia. After surgery, serum CT levels fell to normal. Therefore, a high serum CT can be observed as the consequence of C-cell hyperplasia in Hashimoto's thyroiditis.


Benign neurological recovery with low recurrence and low peridural fibrosis rate in pediatric disc herniations after lumbar microdiscectomy.
Lumbar disc herniation (LDH) is a very rare clinical entity in the pediatric age group, therefore only a few clinical studies have until now investigated the clinical behavior of pediatric LDH. The natural clinical history, postoperative neurological recovery with radiological follow-up and quality of life related to the disorder continue to be unknown. We prospectively planned and designed two groups of LDH patients scheduled for surgery in this study. The operations were performed by the same surgeon in a randomized fashion. The first group consisted of pediatric patients and the second group of adult patients. Both groups contained 32 cases. Postoperative neurological recovery was assessed using the visual analog scale and Aberdeen Low Back Pain Scale. Postoperative peridural fibrosis was also evaluated in postcontrast magnetic resonance sections. After 3 years of follow-up, all parameters were significantly better in the pediatric LDH group with no recurrence of the disease. The pediatric LDH group was postoperatively better than the adult group both clinically and radiologically. Although LDH seems a catastrophic disease in the pediatric age group, the clinical picture and neurological recovery have a significantly more benign course than in adult patients even in operated cases.


[Prerequisites and new approaches toward improving the outpatient registration of mental patients].
An increase in the registered numbers of mental outpatients, particularly at the expense of persons with borderline abnormalities, which is attendant by certain social restrictions for the latter group, is fraught with compromising the personality of these on the whole normal persons, which necessitates reorganization of the existing practice of registering patients in psychoneurological institutions. It is proposed that the existing form of registration be applied only to psychotic patients. In accordance with the level criterion patients with mental disorders of the borderline level are not liable to registration, provided their main links and relations in the social environment have remained intact. Registration should be strictly based on such time limits which can be justified on medico-social and clinico-therapeutical grounds.


SARS CoV 2 infection in chronic myelogenous leukemia: Severe hematological presentation.
Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic. Few data are available about the risk of COVID-19 infection in persons with hematological cancer, but controversy whether these persons have the same clinical signs and outcomes. We describe a case of life-threatening COVID-19 infection complicated by severe anemia in patients affected also by chronic myelogenous leukemia. The screening for RBC antibodies and the direct antiglobulin test (DAT) turned positive. The identification of the antibodies, showed the presence of an alloantibody with anti-Lewis b specificity, which was reactive at room temperature, in the anti-human globulin phase (AGH) and with papain-treated red blood cells. At the same time hemophagocytic lymphohistiocytosis (HLH), on the basis of major laboratory findings including hyperferritnemia, increase of triglicerides levels and according to the HLH score was suspected. Patients received antiviral therapy, steroids and intravenous immunoglobulins. Hemolysis resolved and ferritin dramatically decreased after administration of Ig and a Afull recovery was achieved after viral infection resolution.This case highlights the novel and multifaceted hematological findings during sever COVID 19 infection. COVID 19-related pneumonia is mediated by hyper activation of effector T cells and excessive production of inflammatory cytokines, such as IL-6, IL-1, interferon-gamma, and TNF. This inflammatory process called "cytokine storm" is a life-threatening complication of COVID 19 infection. In this case severe immunohematological consequences are reported for the first time and recognition of this complications are probably underestimated.


Alcohol's Effects on Breast Cancer in Women.
Globally, more than 2 million new cases of breast cancer are reported annually. The United States alone has more than 496,000 new cases every year. The worldwide prevalence is approximately 6.8 million cases. Although many risk factors for breast cancer are not modifiable, understanding the role of the factors that can be altered is critical. Alcohol consumption is a modifiable factor. Studies of alcohol in relation to breast cancer incidence have included hundreds of thousands of women. Evidence is consistent that intake, even intake of less than 10-15 grams per day, is associated with increased risk of this disease. In addition, evidence, although less extensive, shows that possible early indicators of risk, such as benign breast disease and increased breast density, are associated with alcohol consumption. Evidence is less strong for differences based on geographic region, beverage type, drinking pattern, or breast cancer subtype. Some studies have examined the association between alcohol and recurrence or survival after a breast cancer diagnosis. These findings are less consistent. Public awareness of alcohol as a risk factor for breast cancer is low, and public health measures to increase that awareness are warranted.


Magnetizing topological surface states of Bi2Se3 with a CrI3 monolayer.
To magnetize surfaces of topological insulators without damaging their topological feature is a crucial step for the realization of the quantum anomalous Hall effect (QAHE) and remains as a challenging task. Through density functional calculations, we found that adsorption of a semiconducting two-dimensional van der Waals (2D-vdW) ferromagnetic CrI3 monolayer can create a sizable spin splitting at the Dirac point of the topological surface states of Bi2Se3 films. Furthermore, general rules that connect different quantum and topological parameters are established through model analyses. This work provides a useful guideline for the realization of QAHE at high temperatures in heterostructures of 2D-vdW magnetic monolayers and topological insulators.


Conformer aggregates exhibit dual wavelength emissions on chiral binaphthyl-based triphenylethylenes and acetone detection.
The study on structure-property relationship has been a significant focus in the field of organic molecular luminescence. In the present work, three chiral binaphthyl-based triphenylethylene (HTPE) derivatives were prepared through condensation reactions. Despite their similar structures, these compounds exhibited distinct luminescent properties. Diphenylmethane-derived HTPE displayed dual-state emissions, characterized by dual-wavelength emissions which were insensitive to the polarity of solvents. The dual emissions in solution state could be attributed to the different locally excited (LE) excitons. However, upon aggregation, two stable conformers were generated, probably leading to different emission peaks. In contrast, dibenzocycloheptadiene-derived HTPE aggregates showed only a single emission peak. Surprisingly, fluorene-derived HTPE exhibited obvious luminescence in neither solution nor aggregate states due to inherent π-π interactions. These conclusions were substantiated by X-ray analysis, spectroscopic analysis, and theory calculations. Application studies demonstrated that fluorescence on/off switches could be achieved through exposure to acetone. More importantly, trace amounts of acetone could be detected using luminescent materials in both organic and aqueous phases with a detection limit of 0.08%. Thus, this work not only presents a strategy for designing chiral triphenylethylene fluorophores but also provides valuable information for dual wavelength emissions resulting from two stable conformations.


Assessment of an infectious disease history preceding juvenile dermatomyositis symptom onset.
A number of studies have looked at the role of infectious diseases in triggering juvenile dermatomyositis (JDM). Previous studies have found a moderately high frequency of infectious symptoms prior to disease onset; however, no specific pathogens could be identified. We sought to correlate preceding infectious symptoms with onset and outcomes of JDM. We studied an inception cohort of all JDM cases diagnosed at The Hospital for Sick Children (SickKids) between 1988 and 2006. Data pertaining to symptoms at onset, diagnosis and disease outcomes were abstracted. Two independent paediatric infectious disease specialists reviewed all records of patients with symptoms or tests suggestive of infection. A total of 110 patients were reviewed; of these, 78 had sufficient information about disease onset for inclusion. Potential indications of an infectious process prior to JDM onset were found in 55/78 (71%) patients and were further evaluated for evidence of infection temporally associated with symptom onset. Features suggestive of infection prior to JDM symptom onset were found in 40/55 [probable (30/40) or possible (10/40)]. Most children with probable infections had respiratory illnesses [24/30 (80%)]. Fewer patients than expected had disease onset during summer months. The presence of an infection at onset was not found to be associated with differences in characteristics at diagnosis or disease outcomes. A substantial number of JDM patients have a clinical history consistent with an infection prior to onset. Newly diagnosed patients should undergo a full infectious disease assessment as part of their initial work-up; specific attention should be given to respiratory infections.


Genetic modification of alternative respiration has differential effects on antimycin A-induced versus salicylic acid-induced resistance to Tobacco mosaic virus.
Salicylic acid (SA), a natural defensive signal chemical, and antimycin A, a cytochrome pathway inhibitor, induce resistance to Tobacco mosaic virus (TMV). Pharmacological evidence suggested signaling during resistance induction by both chemicals involved alternative oxidase (AOX), sole component of the alternative respiratory pathway (AP). Roles of the AP include regulation of intramitochondrial reactive oxygen species and maintenance of metabolic homeostasis. Transgenic tobacco (Nicotiana tabacum) with modified AP capacities (2- to 3-fold increased or decreased) showed no alteration in phenotype with respect to basal susceptibility to TMV or the ability to display SA-induced resistance to systemic viral disease. However, in directly inoculated tissue, antimycin A-induced TMV resistance was inhibited in plants with increased AP capacities, whereas SA and antimycin A-induced resistance was transiently enhanced in plant lines with decreased AP capacities. We conclude that SA-induced TMV resistance results from activation of multiple mechanisms, a subset of which are inducible by antimycin A and influenced by AOX. Other antiviral factors, potentially including the SA-inducible RNA-dependent RNA polymerase, are regulated by AOX-independent mechanisms.


Combined lateral peripatellar and posteromedial approaches for Schatzker type IV tibial plateau fractures involving posteromedial plane: a prospective study.
The objective of this study to evaluate prospectively the effectiveness of Schatzker type IV tibial plateau fractures involving posteromedial plane managed by combined lateral peripatellar and posteromedial approaches. We analyzed 18 patients with Schatzker type IV tibial plateau fractures involving posteromedial plane. There were 12 males and 6 females with an average of 38.5 years (range, 25-60 years). The mechanism of injury included traffic accident in 15 patients and falling in 3 patients. The injured lower limbs were right in 11 patients and left in 7 patients. The mean time from injury to surgery was 6.78 days (range, 5-9 days). There were 8 patients with meniscus injuries in our study. The mean operation time was 3.41 h (range, 3-4 h). The mean blood loss was 352.78 ml (range, 300-410 ml). All the injured meniscuses were repaired. All patients were followed up, and the average time of follow up was 16.61 months (range, 14-22 months). Bone union was achieved at a mean of 12 weeks (range, 10-14 weeks). The mean degree of knee extension was 1.11° (range, 0-5°), and the mean degree of knee flexion was 120.56° (range, 110-130°). The mean points of KSS were 83 (range, 74-89 points). According to the criteria of KSS, 14 patients had clinical outcomes rated as excellent and 4 patients were rated as good. Our results suggested that Combined lateral peripatellar and posteromedial approaches in the treatment of Schatzker type IV tibial plateau fractures involving posteromedial plane acquired satisfying outcomes. It was good for repairing the injured meniscus through our approaches.


Modified E91 protocol demonstration with hybrid entanglement photon source.
We report on an experimental demonstration of the modified Ekert 91 protocol of quantum key distribution using a hybrid entanglement source with two different degrees of freedoms, a 1550 nm time-bin qubit and 810 nm polarization qubit. The violation of the Clauser-Horne-Shimony-Holt inequality could be demonstrated for the entanglement between the polarization qubit in free space and the time-bin qubit through 20 km fiber transmission. The secure key rate in our system is estimated 70-150 bps.


Agroinfection-based high-throughput screening reveals specific recognition of INF elicitins in Solanum.
SUMMARY We adapted and optimized the use of the Agrobacterium tumefaciens binary PVX expression system (PVX agroinfection) to screen Solanum plants for response to pathogen elicitors and applied the assay to identify a total of 11 clones of Solanum huancabambense and Solanum microdontum, out of 31 species tested, that respond to the elicitins INF1, INF2A and INF2B of Phytophthora infestans. Prior to this study, response to INF elicitins was only known in Nicotiana spp. within the Solanaceae. The identified S. huancabambense and S. microdontum clones also exhibited hypersensitivity-like cell death following infiltration with purified recombinant INF1, INF2A and INF2B, thereby validating the screening protocol. Comparison of INF elicitin activity revealed that Nicotiana plants responded to significantly lower concentrations than Solanum, suggesting variable levels of sensitivity to INF elicitins. We exploited natural variation in response to INF elicitins in the identified Solanum accessions to evaluate the relationship between INF recognition and late blight resistance. Interestingly, several INF-responsive Solanum plants were susceptible to P. infestans. Also, an S. microdontum xSolanum tuberosum (potato) population that segregates for INF response was generated but failed to identify a measurable contribution of INF response to resistance. These results suggest that in Solanum, INF elicitins are recognized as general elicitors and do not have a measurable contribution to disease resistance.


[Water channels of the cell--aquaporins].
Several mechanisms in the body regulate the water transport within the cells up and down during physiological and pathological conditions. The discovery of aquaporins, water channel proteins, has brought more insight into and understanding of how water crosses plasma membranes within cells in body tissue. The functions of aquaporins are not fully understood; this paper summarise current knowledge of various aquaporins. Known aquaporins are discussed in relation to some physiological, pathological and clinical conditions. In the future, measurements of aquaporin concentrations in urine and possibly in other samples will give us a broader picture of water exchange and a better understanding of the mechanisms underlying water production in clinical states like renal and heart failure and liver insufficiency. Moreover, by manipulating water channel proteins by compounds developed for this purpose, one may have a tool for treating some clinical disorders in which water depletion or water overload is an important factor.


An outbreak of acute bacterial gastroenteritis is associated with an increased incidence of irritable bowel syndrome in children.
Acute bacterial gastroenteritis is associated with subsequent post-infectious irritable bowel syndrome (PI-IBS) in adults. Less is known about this relationship in children. In May 2000, contamination of municipal water by Escherichia coli 0157:H7 and Campylobacter species caused a large outbreak of acute gastroenteritis in Walkerton, Ontario. We assessed this association among a cohort of children enrolled in the Walkerton Health Study (WHS). WHS participants who were under age 16 at the time of the outbreak but who reached age 16 during the 8-year study follow-up were eligible for the pediatric PI-IBS study cohort. Eligibility also required no diagnosis of IBS or inflammatory bowel disease before the outbreak and permanent residency in the Walkerton postal code at the time of the outbreak. Validated criteria were used to classify subjects as having had no gastroenteritis (unexposed controls), self-reported gastroenteritis, or clinically suspected gastroenteritis during the outbreak. From 2002 to 2008, standardized biennial interviews used a modified Bowel Disease Questionnaire to diagnose IBS by Rome I criteria. Risk factors for IBS were identified by logistic regression. In all, 467 subjects were eligible for the pediatric PI-IBS study cohort (47.1% female; mean age 11.6+/-2.44 years at the time of the outbreak). Of these, 305 were exposed to GE (130 clinically suspected and 175 self-reported) and 162 were unexposed controls. The cumulative incidence of IBS was significantly increased among exposed subjects vs. controls (10.5% vs. 2.5%; odds ratio 4.6, 95% confidence interval (1.6, 13.3)). In an unadjusted risk factor analysis, IBS was associated with a shorter time interval from exposure to assessment of IBS symptoms, female gender, diarrheal illness lasting more than 7 days, weight loss >10 lb, and antibiotic use during the outbreak. In adjusted analyses, both female gender and time interval to assessment of IBS symptoms remained independent predictors of PI-IBS. Acute bacterial gastroenteritis is associated with subsequent IBS in children as in adults. Risk factors for PI-IBS in children are similar to those identified among adults. Confirmation of these findings in similar cohorts is needed.


Thorium-nitrogen multiple bonds provide evidence for pushing-from-below for early actinides.
Although the chemistry of uranium-ligand multiple bonding is burgeoning, analogous complexes involving other actinides such as thorium remain rare and there are not yet any terminal thorium nitrides outside of cryogenic matrix isolation conditions. Here, we report evidence that reduction of a thorium-azide produces a transient Th≡N triple bond, but this activates C-H bonds to produce isolable parent imido derivatives or it can be trapped in an N-heterocycle amine. Computational studies on these thorium-nitrogen multiple bonds consistently evidences a σ > π energy ordering. This suggests pushing-from-below for thorium, where 6p-orbitals principally interact with filled f-orbitals raising the σ-bond energy. Previously this was dismissed for thorium, being the preserve of uranium-nitrides or the uranyl dication. Recognising that pushing-from-below perhaps occurs with thorium as well as uranium, and with imido ligands as well as nitrides, suggests this phenomenon may be more widespread than previously thought.


Isolation and sequencing of a cDNA clone homologous to the v-sis oncogene from human endothelial cells.
A clone containing the 3' end of the mRNA for the human c-sis gene (homologous to the B chain of platelet-derived growth factor) was isolated from a cDNA library derived from human umbilical vein endothelial cells and then sequenced. The analysis of possible translation products in all three reading frames indicated that the A chain of platelet-derived growth factor was not coded for within the 3' end of the c-sis mRNA. The 3' end of the mRNA for c-sis is contained in or adjacent to exon 6.


Grazing-incidence Mirror System for Use with a Grating Spectrometer in the Extreme Ultraviolet.
This paper describes the design of a two-component grazing-incidence mirror system for use with a grazing-incidence spectrometer in order to record spatially resolved solar spectra in the 150-850-A region. Photoelectric measurements are presented of the point spread function and reflectivity of the mirror system at discrete wavelengths in the extreme ultraviolet.


Molecular structure and transcriptional function of the rat vascular AT1a angiotensin receptor gene.
Rat vascular angiotensin receptors (AT1a receptors) are encoded by two mRNA transcripts sharing an identical receptor coding sequence but differing in their 5' and 3' untranslated sequences. We screened male Sprague-Dawley rat genomic libraries to clone the vascular AT1a receptor gene. Two sets of overlapping clones were isolated that encode over 90 kb of genomic sequence around the AT1a receptor gene. Four overlapping clones were identified from the 5' flanking portion of the gene. These contain the promoter region and two exons, 141 bp and 89 bp in size, respectively, encoding the alternatively spliced 5' untranslated mRNA sequence. Six additional clones overlap each other but do not overlap the set of clones from the 5' flanking region of the gene. These contain a single 1977-bp exon that encodes 900 bp of the 5' and 3' untranslated sequences in addition to a 1077-bp open reading frame identical to that found in vascular smooth muscle cell AT1a receptor cDNAs. Primer extension and RNase protection studies indicate that the transcription start site for this gene begins 9 bp upstream from the most 5' sequence found within the AT1a receptor cDNAs. Our mapping studies of the cloned gene, which so far includes an uncloned gap within the second intron, indicate that the transcription start site is no less than 67 kb upstream from the receptor coding exon. Promoter-reporter assays were performed by transfection of vascular smooth muscle cells with deletions of a 3.2-kb promoter region fused to a luciferase cDNA reporter plasmid. Relatively strong basal transcriptional activity is observed from the 5'-most 2 kb of the promoter and diminishes markedly with deletions within 1 kb of the early promoter region, suggesting strong promoter elements in the more upstream regions of the gene. Deletion of a 53-bp early promoter region containing the transcription start site and a putative TATA box completely abolishes the ability of upstream elements to drive transcription of the luciferase cDNA. These results indicate that we have isolated the AT1a receptor gene and its functional promoter.


The role of cell adhesion molecule in cancer progression and its application in cancer therapy.
Multiple and diverse cell adhesion molecules take part in intercellular and cell-extracellular matrix interactions of cancer. Cancer progression is a multi-step process in which some adhesion molecules play a pivotal role in the development of recurrent, invasive, and distant metastasis. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of cancer. Loss of intercellular adhesion and the desquamation of cells from the underlying lamina propria allows malignant cells to escape from their site of origin, degrade the extracellular matrix, acquire a more motile and invasion phenotype, and finally, invade and metastasize. In addition to participating in tumor invasiveness and metastasis, adhesion molecules regulate or significantly contribute to a variety of functions including signal transduction, cell growth, differentiation, site-specific gene expression, morphogenesis, immunologic function, cell motility, wound healing, and inflammation. Cell adhesion molecule (CAM), a diverse system of transmembrane glycoproteins has been identified that mediates the cell-cell and cell-extracellular matrix adhesion and also serves as the receptor for different kinds of virus. We summarize recent progress regarding the role of CAM, particularly, immunoglobulin-CAMs and cadherins in the progression of cancer and discuss the potential application of CAMs in the development of cancer therapy mainly on urogenital cancer.


Combined but Not Isolated Ingestion of Caffeine and Taurine Improves Wingate Sprint Performance in Female Team-Sport Athletes Habituated to Caffeine.
Previous studies have investigated caffeine (CAF) and taurine (TAU) in isolation and combined during exercise in males. However, the potential synergistic effect during high-intensity exercise remains unknown in female athletes. Seventeen female team-sport athletes participated (age: 23.4 ± 2.1 years; height: 1.68 ± 0.05 m; body mass: 59.5 ± 2.2 kg). All participants were habitual caffeine consumers (340.1 ± 28.6 mg/day). A double-blind randomized crossover design was used. Participants completed four experimental trials: (i) CAF and TAU (6 mg/kg body mass of CAF + 1 g of TAU), (ii) CAF alone; (iii) TAU alone; and (iv) placebo (PLA). Supplements were ingested 60 min before a 30-s Wingate Anaerobic Test (WAnT). Heart rate and blood lactate (BL) were measured before and immediately after the WAnT; and ratings of perceived exertion (RPE) were recorded immediately after the WAnT. Peak power (PP) was significantly higher following co-ingestion of CAF+TAU compared to PLA (p = 0.03) and TAU (p = 0.03). Mean power (MP) was significantly higher following co-ingestion of CAF+TAU compared to PLA (p = 0.01). No other differences were found between conditions for PP and MP (p > 0.05). There were also no observed differences in fatigue index (FI), BL; heart rate; and RPE between conditions (p > 0.05). In conclusion, compared to PLA the combined ingestion of 6 mg/kg of CAF and 1 g of TAU improved both PP and MP in female athletes habituated to caffeine; however; CAF and TAU independently failed to augment WAnT performance.


Temporary Self-Deprivation Can Impair Cognitive Control: Evidence From the Ramadan Fast.
During Ramadan, people of Muslim faith fast by not eating or drinking between sunrise and sunset. This is likely to have physiological and psychological consequences for fasters, and societal and economic impacts on the wider population. We investigate whether, during this voluntary and temporally limited fast, reminders of food can impair the fasters' reaction time and accuracy on a non-food-related test of cognitive control. Using a repeated measures design in a sample of Ramadan fasters (N = 190), we find that when food is made salient, fasters are slower and less accurate during Ramadan compared with after Ramadan. Control participants perform similarly across time. Furthermore, during Ramadan performances vary by how recently people had their last meal. Potential mechanisms are suggested, grounded in research on resource scarcity, commitment, and thought suppression, as well as the psychology of rituals and self-regulation, and implications for people who fast for religious or health reasons are discussed.


The role of domain-specific and domain-general cognitive functions and skills in sports performance: A meta-analysis.
Cognition plays a key role in sports performance. This meta-analytic review synthesizes research that examined the relationship between cognitive functions, skills, and sports performance. We identified literature by searching Cochrane Library, APA PsycINFO, PubMed, and Web of Science. We included studies conducted on competitive athletes, assessed cognitive prerequisites, and included performance measures related to the sport. Of the 9,433 screened records, 136 reports were included, containing 142 studies, 1,227 effect sizes, and 8,860 participants. Only 11 studies used a prospective study design. The risk of bias was assessed using the Risk of Bias Assessment Tool for Nonrandomized Studies. The multilevel meta-analysis showed a medium effect size for the overall difference in cognitive functions and skills, with higher skilled athletes scoring better than lower skilled athletes (Hedges' g = 0.59, 95% CI [0.49, 0.69]). The moderator analysis showed larger effect size for tests of cognitive decision-making skills (g = 0.77, 95% CI [0.6, 0.94]) compared to basic (g = 0.39, 95% CI [0.21, 0.56]) and higher cognitive functions (g = 0.44, 95% CI [0.26, 0.62]), as well as larger effect for sport-specific task stimuli compared to general ones. We report that higher skilled athletes perform better on cognitive function tests than lower skilled athletes. There was insufficient evidence to determine whether cognitive functions and skills can predict future sport performance. We found no evidence to support claims that tests of general cognitive functions, such as executive functioning, should be used by practitioners for talent identification or player selection. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Salivary gland choristoma of the middle ear. A review.
While head and neck surgeons are accustomed to recognizing malignancies in their practices, developmental lesions are much less often encountered, and as such are not as likely to be included amongst other (more aggressive) differential diagnostic considerations. One such developmental lesion is the choristoma, defined as an architecturally normal arrangement of mature tissues found in a location not normally host to such tissues. Choristomas composed of recognizable salivary gland tissue may be found in a variety of locations including the middle ear. Middle ear salivary choristomas are distinctly unusual lesions and typically manifest as unilateral conductive hearing loss; while both adult and pediatric patients have been diagnosed with middle ear choristomas, most patients have been in the first two decades of life. As these are benign, nonprogressive lesions, treatment has been directed toward complete surgical excision whenever feasible, and biopsy for diagnosis with subsequent observation in the case of those lesions which are difficult to remove without endangering the facial nerve. There have been rare instances in which choristomas have been linked to the subsequent development of neoplasms, but in the main choristomas are regarded as self-limited developmental heterotopias.


Altered thyroid axis function in Lewis rats with genetically defective hypothalamic CRH/VP neurosecretory cells.
Lewis rats display hyporesponsive hypothalamo-pituitary-adrenocortical (HPA) axes, overproduction of cytokines, and susceptibility to inflammatory disease. The Lewis corticotropin-releasing hormone (CRH) neurosecretory system contains normal numbers of vasopressin (VP)-deficient axon varicosities, but abnormally sparse VP-containing varicosities in the external zone of the median eminence, compared to the normoresponsive Sprague Dawley (SD), Wistar and Fischer 344 strains. Since VP may act as a thyrotropin-releasing factor, we hypothesized that thyroid axis responsivity may be altered in Lewis rats. T3, T4 and TSH were measured by radioimmunoassay, and free T4 by equilibrium dialysis, in adult male Lewis and SD rats. One h cold (5 degrees C) induced significant increases in T3, T4 and TSH levels in Lewis rats but not in SD rats. Ninety min insulin-induced hypoglycemia (1 IU/kg, i.p.) induced a significant T3 increase in Lewis rats and a significant T4 increase in SD rats. Two h after ip LPS (0.25 or 0.75 mg/kg), T4 levels fell significantly in Lewis rats but not in SD rats. TSH decreases were significant in Lewis rats after 0.75 mg/kg and in SD rats after 0.25 mg/kg. Baseline hormone levels were generally higher in Lewis rats; the differences were significant for T3 and T4 in the insulin experiments and for T3, T4 and free T4 in the LPS experiments. The data suggest that reduced inhibition from the adrenocortical axis in Lewis rats leads to hyperresponsivity of the thyroid axis to cold, and greater LPS-induced decreases in T4 levels, probably due to an exaggerated inhibitory cytokine response.


Predicting trace organic compound attenuation by ozone oxidation: Development of indicator and surrogate models.
Ozone oxidation has been demonstrated to be an effective treatment process for the attenuation of trace organic compounds (TOrCs); however, predicting TOrC attenuation by ozone processes is challenging in wastewaters. Since ozone is rapidly consumed, determining the exposure times of ozone and hydroxyl radical proves to be difficult. As direct potable reuse schemes continue to gain traction, there is an increasing need for the development of real-time monitoring strategies for TOrC abatement in ozone oxidation processes. Hence, this study is primarily aimed at developing indicator and surrogate models for the prediction of TOrC attenuation by ozone oxidation. To this end, the second-order kinetic equations with a second-phase Rct value (ratio of hydroxyl radical exposure to molecular ozone exposure) were used to calculate comparative kinetics of TOrC attenuation and the reduction of indicator and spectroscopic surrogate parameters, including UV absorbance at 254 nm (UVA254) and total fluorescence (TF). The developed indicator model using meprobamate as an indicator compound and the surrogate models with UVA254 and TF exhibited good predictive power for the attenuation of 13 kinetically distinct TOrCs in five filtered and unfiltered wastewater effluents (R2 values > 0.8). This study is intended to help provide a guideline for the implementation of indicator/surrogate models for real-time monitoring of TOrC abatement with ozone processes and integrate them into a regulatory framework in water reuse.


Challenges with developing in vitro dissolution tests for orally inhaled products (OIPs).
The purpose of this article is to review the suitability of the analytical and statistical techniques that have thus far been developed to assess the dissolution behavior of particles in the respirable aerodynamic size range, as generated by orally inhaled products (OIPs) such as metered-dose inhalers and dry powder inhalers. The review encompasses all analytical techniques publicized to date, namely, those using paddle-over-disk USP 2 dissolution apparatus, flow-through cell dissolution apparatus, and diffusion cell apparatus. The available techniques may have research value for both industry and academia, especially when developing modified-release formulations. The choice of a method should be guided by the question(s) that the research strives to answer, as well as by the strengths and weaknesses of the available techniques. There is still insufficient knowledge, however, for translating the dissolution data into statements about quality, performance, safety, or efficacy of OIPs in general. Any attempts to standardize a dissolution method for compendial inclusion or compendial use would therefore be premature. This review reinforces and expands on the 2008 stimulus article of the USP Inhalation Ad Hoc Advisory Panel, which "could not find compelling evidence suggesting that such dissolution testing is kinetically and/or clinically crucial for currently approved inhalation drug products."


Meiotic Cas9 expression mediates gene conversion in the male and female mouse germline.
Highly efficient gene conversion systems have the potential to facilitate the study of complex genetic traits using laboratory mice and, if implemented as a "gene drive," to limit loss of biodiversity and disease transmission caused by wild rodent populations. We previously showed that such a system of gene conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double-strand DNA break (DSB) is feasible in the female mouse germline. In the male germline, however, all DSBs were instead repaired by end joining (EJ) mechanisms to form an "insertion/deletion" (indel) mutation. These observations suggested that timing Cas9 expression to coincide with meiosis I is critical to favor conditions when homologous chromosomes are aligned and interchromosomal homology-directed repair (HDR) mechanisms predominate. Here, using a Cas9 knock-in allele at the Spo11 locus, we show that meiotic expression of Cas9 does indeed mediate gene conversion in the male as well as in the female germline. However, the low frequency of both HDR and indel mutation in both male and female germlines suggests that Cas9 may be expressed from the Spo11 locus at levels too low for efficient DSB formation. We suggest that more robust Cas9 expression initiated during early meiosis I may improve the efficiency of gene conversion and further increase the rate of "super-mendelian" inheritance from both male and female mice.


Characterization of a positive regulatory gene, LAC9, that controls induction of the lactose-galactose regulon of Kluyveromyces lactis: structural and functional relationships to GAL4 of Saccharomyces cerevisiae.
Lactose or galactose induces the expression of the lactose-galactose regulon in Kluyveromyces lactis. We show here that the regulon is not induced in strains defective in LAC9. We demonstrate that this gene codes for a regulatory protein that acts in a positive manner to induce transcription. The LAC9 gene was isolated by complementation of a lac9 defective strain. DNA sequence analysis of the gene gave a deduced protein of 865 amino acids. Comparison of this sequence with that of the GAL4 protein of Saccharomyces cerevisiae revealed three regions of homology. One region of about 90 amino acid occurs at the amino terminus, which is known to mediate binding of GAL4 protein to upstream activator sequences. We speculate that a portion of this region, adjacent to the "metal-binding finger," specifies DNA binding. We discuss possible functions of the two other regions of homology. The functional implications of these structural similarities were examined. When LAC9 was introduced into a gal4 defective strain of S. cerevisiae it complemented the mutation and activated the galactose-melibiose regulon. However, LAC9 did not simply mimic GAL4. Unlike normal S. cerevisiae carrying GAL4, the strain carrying LAC9 gave constitutive expression of GAL1 and MEL1, two genes in the regulon. The strain did show glucose repression of the regulon, but repression was less severe with LAC9 than with GAL4. We discuss the implications of these results and how they may facilitate our understanding of the LAC9 and GAL4 regulatory proteins.


CTRP is essential for mosquito infection by malaria ookinetes.
The malaria parasite suffers severe population losses as it passes through its mosquito vector. Contributing factors are the essential but highly constrained developmental transitions that the parasite undergoes in the mosquito midgut, combined with the invasion of the midgut epithelium by the malaria ookinete (recently described as a principal elicitor of the innate immune response in the Plasmodium-infected insect). Little is known about the molecular organization of these midgut-stage parasites and their critical interactions with the blood meal and the mosquito vector. Elucidation of these molecules and interactions will open up new avenues for chemotherapeutic and immunological attack of parasite development. Here, using the rodent malaria parasite Plasmodium berghei, we identify and characterize the first microneme protein of the ookinete: circumsporozoite- and TRAP-related protein (CTRP). We show that transgenic parasites in which the CTRP gene is disrupted form ookinetes that have reduced motility, fail to invade the midgut epithelium, do not trigger the mosquito immune response, and do not develop further into oocysts. Thus, CTRP is the first molecule shown to be essential for ookinete infectivity and, consequently, mosquito transmission of malaria.


Expression of albumin messenger RNA detected by in situ hybridization in preneoplastic and neoplastic lesions in rat liver.
The process of chemical hepatocarcinogenesis is characterized by the appearance of preneoplastic lesions showing changes in the expression of various marker enzymes. We have analyzed the phenotype of small preneoplastic foci and expansively growing nodules in liver sections obtained from rats treated with various carcinogens. Changes within the lesions in canalicular adenosine triphosphatase, gamma-glutamyl transpeptidase, NADPH-(cytochrome P-450) reductase, cytochrome P-450 PB2, epoxide hydrolase, and glycogen content were detected by means of enzyme histochemical and immunohistochemical staining procedures. In parallel sections the expression of albumin messenger RNA was investigated by in situ hybridization using a 35S-labeled albumin specific complementary DNA probe. In general, small preneoplastic lesions showed unchanged levels of albumin messenger RNA. In contrast, the expression of albumin messenger RNA was found to be reduced to varying degrees in large hepatic nodules. An expression of alpha-fetoprotein messenger RNA could not be detected in any of the nodules. No direct correlation between the enzyme phenotype of the lesions and the degree in reduction of albumin messenger RNA could be established except that the reduction was most pronounced in nodules which had lost their ability to store glycogen. Since the synthesis and excretion of albumin is a typical function of the differentiated hepatocyte in the adult animal, the observed decrease in albumin messenger RNA expression in large hepatic nodules is in accordance with the hypothesis of a gradual dedifferentiation or retrodifferentiation of the cell population during carcinogenesis. Hyperplastic nodules produced by continuous treatment of rats with 4-dimethylaminoazobenzene showed increased rather than decreased albumin levels. The analysis of albumin messenger RNA expression might therefore be used as a tool to discriminate between nodules of differing biological nature and fate.


Child mortality and HIV infection in Africa: a review.
To review the available data relating to child mortality in Africa by the HIV infection status of mothers and children. Child survival is influenced by the HIV epidemic through several mechanisms. Mother-to-child transmission of HIV ranges from 15 to 45%, with up to 15-20% resulting from breastfeeding. HIV-infected children have high mortality rates. For example, a recent community-based study in Rakai, Uganda, showed 2-year mortality rates of 547, 166 and 128 per thousand among HIV-infected children, HIV-negative children of HIV-positive mothers, and HIV-negative children of HIV-negative women, respectively. Child mortality estimates from community-based cohorts demonstrate that the children of HIV-infected mothers have higher mortality rates than the children of uninfected mothers, and that child mortality is closely linked with maternal health status, but because the proportion of vertically infected children is unknown, the value of these studies is limited. Models that use HIV surveillance data together with a set of assumptions indicate that child mortality caused by HIV/AIDS has increased throughout the 1990s to reach close to 10% by 2002. Both disparate trends in HIV prevalence and varying levels of non-HIV-associated child mortality will ensure very different impacts in different countries. To improve the projections of the overall effect that the HIV epidemic will have on child mortality at the population level in countries with generalized epidemics, reliable age-specific mortality rates in infected and uninfected children are needed.


Effect of decalcification agents on immunoreactivity of cellular antigens.
The effects of several strong acids, weak acids, a proprietary decalcifier, and edetic acid on the immunohistochemical staining of cryostat and fixed paraffin embedded sections of tissue from a variety of normal and pathological calcified and uncalcified specimens were studied. Even decalcification in strong acids (HCl, HN03, 5% trichloracetic acid, HCl-edetic acid did not diminish the reactivity of many useful antigens (including leucocyte common antigen, intermediate filaments, S100 protein and epithelial membrane antigen). Weaker acids (formic acid, acetic acid) and edetic acid decalcified more slowly and generally showed greater preservation of antigenic reactivity with better morphology and staining quality. Trichloracetic acid was also useful as a quick one step fixation and decalcifying agent for both cryostat and routinely processed sections. Knowledge of the preservation of antigenic reactivity in decalcified tissue will be useful in the diagnosis of tumours of uncertain histogenesis and origin which affect calcified tissues.


Tremor at onset. Predictor of cognitive and motor outcome in Parkinson's disease?
We examined 46 male patients with idiopathic Parkinson's disease to see whether tremor at onset was as useful a predictor of benign clinical outcome as tremor predominance after several years. When we compared patients with tremor at onset (n = 27) with those whose disease began with brady-kinesia/rigidity (n = 9), or gait disorder (n = 10), we found no significant differences after a mean of 7 years in motor, cognitive, or affective status. Sixteen of the tremor-onset patients continued to have tremor predominance with minimal gait disorder after about 7 years. These tremor-predominant patients had significantly better motor outcome and somewhat better cognitive outcome than either tremor-onset patients who subsequently developed gait disorder (n = 11) or patients without tremor at onset (n = 19). Tremor predominance after several years appears to be a better predictor of a benign clinical course of Parkinson's disease than tremor at onset.


A longitudinal study of the relationship between personality traits and the annual rate of volume changes in regional gray matter in healthy adults.
To investigate whether personality traits affect the rate of decline of gray matter volume, we analyzed the relationships between personality traits and the annual rate of changes of gray matter volume in 274 healthy community dwelling subjects with a large age range by applying a longitudinal design over 6 years, using brain magnetic resonance images (MRI) and the Revised NEO Personality Inventory (NEO-PI-R) at baseline. Brain MRI data were processed using voxel-based morphometry with a custom template by applying the DARTEL diffeomorphic registration tool. For each subject, we used NEO-PI-R to evaluate the five major personality traits, including neuroticism, extraversion, openness, agreeableness, and conscientiousness. The results show that the annual rate of change in regional gray matter volume in the right inferior parietal lobule was correlated significantly and negatively with a personality of openness, which is known to be related to intellect, intellectual curiosity, and creativity adjusting for age, gender, and intracranial volume. This result indicates that subjects with a personality trait of less openness have an accelerated loss of gray matter volume in the right inferior parietal lobule, compared with subjects with a personality trait of more openness. Because the right inferior parietal lobule is involved in higher cognitive function such as working memory and creativity, a personality trait of openness is thought to be important for preserving gray matter volume and cognitive function of the right inferior parietal lobule in healthy adults.


New insights into the karyotype evolution of the free-living flatworm Macrostomum lignano (Platyhelminthes, Turbellaria).
The free-living flatworm Macrostomum lignano is a model organism for evolutionary and developmental biology studies. Recently, an unusual karyotypic diversity was revealed in this species. Specifically, worms are either 'normal' 2n = 8, or they are aneuploid with one or two additional large chromosome(s) (i.e. 2n = 9 or 2n = 10, respectively). Aneuploid worms did not show visible behavioral or morphological abnormalities and were successful in reproduction. In this study, we generated microdissected DNA probes from chromosome 1 (further called MLI1), chromosome 2 (MLI2), and a pair of similar-sized smaller chromosomes (MLI3, MLI4). FISH using these probes revealed that MLI1 consists of contiguous regions homologous to MLI2-MLI4, suggesting that MLI1 arose due to the whole genome duplication and subsequent fusion of one full chromosome set into one large metacentric chromosome. Therefore, one presumably full haploid genome was packed into MLI1, leading to hidden tetraploidy in the M. lignano genome. The study of Macrostomum sp. 8 - a sibling species of M. lignano - revealed that it usually has one additional pair of large chromosomes (2n = 10) showing a high homology to MLI1, thus suggesting hidden hexaploidy in its genome. Possible evolutionary scenarios for the emergence of the M. lignano and Macrostomum sp. 8 genomes are discussed.


Ventilator-associated pneumonia prevention methods using topical antibiotics: herd protection or herd peril?
Ventilator-associated pneumonia (VAP) develops in approximately 20% of patients in the ICU receiving prolonged mechanical ventilation (MV). Among the range of methods for preventing VAP, the evidence base for topical antibiotics (TAs), including selective digestive decontamination, appears to be the most compelling. However, several observations are puzzling, and the contextual influence resulting from concurrent use of both topical placebo and TA within an ICU remains untested. As with herd protection conferred by vaccination, contextual influences resulting from a population-based intervention cannot be estimated at the level of a single trial. Estimating contextual effects requires multilevel random-effects methods. In this way the dispersion in VAP incidence across groups from 206 studies, as cited in various-source systematic reviews, was calibrated. The benchmark mean VAP incidence derived from 49 observational groups of patients receiving MV is 23.7% (95% CI, 20.6%-27.2%). In contrast, for 20 and 15 concurrent control groups from the TA evidence base that did vs did not receive topical placebo, respectively, this incidence is 38% (95% CI, 29%-48%) and 33% (95% CI, 20%-50%). This contextual influence remains significant in a meta-regression model adjusted for group-level variables, such as within a trauma ICU context. The mean VAP incidence for five other categories of control groups from the broader evidence base is within four percentage points of the benchmark. The contextual effect of TA is paradoxic, peculiar, potent, perfidious, and potentially perilous. The TA evidence base requires reappraisal to consider this herd peril.


The use of multiplex real-time PCR improves the detection of the bacterial etiology of community acquired pneumonia.
Community-acquired pneumonia (CAP) is still a major cause of morbidity and mortality especially to children and compromised hosts, such as the old and those with underlying chronic diseases. Knowledge of pathogens causing CAP constitutes the basis for selection of antimicrobial treatment. Previous data have shown that etiological agents can be identified in only up to 50% of patients, but this figure can be improved by using polymerase chain reaction (PCR). This study was designed to evaluate multiplex real-time PCR as a method for rapid differential detection of five bacterial causes of CAP (Streptococcus pneumoniae, Burkholderia pseudomallei and atypical bacterial pathogens namely Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila) in CAP patients attending Hospital Tengku Ampuan Afzan (HTAA)/ Kuantan, Pahang, Malaysia. Two previously developed multiplex real-time PCR assays, duplex for the differential detection of S. pneumoniae and B. pseudomallei and triplex for the atypical bacterial pathogens, were used to detect a bacterial cause of CAP in blood and respiratory samples. Thus, 46 blood and 45 respiratory samples collected from 46 adult CAP patients admitted to HTAA were analysed by multiplex real-time PCR assays and conventional methods. The microbial etiology of CAP could be established for 39.1% (18/46) of CAP patients by conventional methods and this was increased to 65.2% (30/46) with the additional use of real-time PCR. The most frequently detected pathogens were S. pneumoniae (21.7% - all by PCR alone), Klebsiella pneumoniae (17.3%), B. pseudomallei (13% - 83% of them positive by PCR alone and 17% by both culture and PCR), Pseudomonas aeruginosa (6.5%), M. pneumoniae (6.5% - all by serology), C. pneumoniae (4.3% - all positive by both PCR and serology), L. pneumophila (2.1% - all by PCR alone), Escherichia coli (4.3%). Haemophilus infuenzae, Acinetobacter lwoffii and Acinetobacter baumannii were detected by conventional methods (2.1% for each).


Malignant melanoma of the skin in Upstate New York: recent trends and characteristics.
Some descriptive epidemiologic characteristics, and recent trends in incidence rates, were analyzed for 2,818 malignant melanomas of the skin diagnosed among residents of Upstate New York (ie, New York State exclusive of New York City) in 1975-1979 and reported to the population-based New York State Cancer Registry. For later clinical-stage melanomas, higher incidence rates among males vs females indicate the need for earlier detection among males. Higher total melanoma incidence rates in younger (less than or equal to 44 years) females vs males were due to higher rates for clinical-stage 1 melanomas, indicating the need for primary prevention. For both males and females, the proportion of cases diagnosed at early clinical stage (ie, stage 1) was lower in single vs married cases, although differences were not statistically significant. The proportion of clinical stage 1 melanomas was significantly lower among widowed vs married women, indicating another target group for secondary prevention. Incidence rates and median household income by county were significantly associated (rank-order correlation test) for males aged 55-64 and females age 65 + years. Recent increases (from 1975 to 1979) in melanoma incidence rates were greater for clinical stage 1 (vs stages 2-3) melanomas and for males vs females; rates for stage 1 melanomas of the trunk in males increased 74.5% over the period (1975 to 1979). Such descriptive data should be useful in planning public education and cancer screening programs.


Expression of CA125 and cisplatin susceptibility of pleural effusion-derived human lung cancer cells from a Thai patient.
Advances in understanding lung cancer biology and tumor markers aid clinicians in managing the disease. Cancer-associated antigen (CA)125 has garnered increasing attention in lung cancer research and may benefit the treatment and follow-up of this type of cancer. In Thai lung cancer patients, knowledge regarding ethnic differences in cancer cell biology is largely absent. We generated lung cancer cells from the pleural effusion fluids of a Thai patient and designated these as P1 cells. P1 cells were assessed for growth rate, response to chemotherapy, and the presence of tumor markers, in particular CA125 expression. Results of immunofluorescence indicated that P1 cells exhibited strong expression levels of CA125, comparable to that of established H460 lung cancer cells. Furthermore, P1 cells were analyzed for the expression of additional markers. Results revealed that H460 cells exhibited strong immunofluorescent signals from cytokeratin-19 fragments (CYFRA 21-1) and squamous cell carcinoma antigen (SCCA) while P1 presented only CYFRA 21-1 signals. We also found evidence of relative cisplatin resistance in P1 compared to the susceptibility level of established lung cancer cells. Thus, the results and methodology described in this study may aid the development of lung cancer diagnostic and therapeutic approaches and, in particular, advance understanding of ethnic differences.


Biodiversity inhibits species' evolutionary responses to changing environments.
Despite growing interplay between ecological and evolutionary studies, the question of how biodiversity influences evolutionary dynamics within species remains understudied. Here, using a classical model of phenotypic evolution in species occupying a patchy environment, but introducing global change affecting patch conditions, we show that biodiversity can inhibit species' evolution during global change. The presence of several species increases the chance that one or more species are pre-adapted to new conditions, which restricts the ecological opportunity for evolutionary responses in all the species. Consequently, environmental change tends to select for changes in species abundances rather than for changing phenotypes within each species. The buffering effects of species diversity that we describe might be one important but neglected explanation for widely observed niche conservatism in natural systems. Furthermore, the results show that attempts to understand biotic responses to environmental change need to consider both ecological and evolutionary processes in a realistically diverse setting.


Treatment of Unstable Elbow Injuries with a Hinged Elbow Fixator: Subjective and Objective Results.
Injuries around the elbow pose a challenging problem for orthopaedic surgeons. The complex bony architecture of the joint should be restored and the thin soft tissue envelope needs to be handled with meticulous care. Elbow instability is a complication seen after dislocations and fractures of the elbow and remains a treatment challenge. The purpose of this study was to provide subjective and objective results following the surgical treatment of unstable elbow dislocations with an external hinged fixation technique. Forty-six consecutive patients with complex trauma of the elbow with instability after ligament reconstruction were enrolled between January 2017 and December 2019. The parameters used to quantify the subjective and objective functional results were the Mayo Elbow Score (MES, objective) and Oxford Elbow Score (OES, subjective), and clinical stability of the elbow joint. We also performed a radiological follow-up of the fractures. The mean MES and OES scores were good at the 12-month follow-up. We had 38 patients with stable joints and 8 patients with minor instability. Using the stress test, we saw a significant difference in the affected joint under varus stress (6.7 ± 1.8 mm) compared to the healthy joint (5.8 ± 1.2 mm) laterally. Furthermore, medially the gap was significantly larger (5.8 ± 0.8 mm, treated elbow) than the contralateral gap under valgus stress (4.3 ± 0.8 mm) (p <0.001). Twenty-one complications occurred in 46 patients (46%): Seven patients had a clinical change of elbow axis: Three valgus (6%), four varus (9%); Superficial wound infection occurred in one case (2%) and ulnar nerve dysfunction in two (4%). The most common medium-term complication was post-traumatic osteoarthritis in eight cases (17%). Heterotopic ossification occurred in five patients (11%) and elbow stiffness in five cases (11%). The use of the hinged elbow external fixator in the treatment of complex elbow trauma is a valid therapeutic adjunct to ligamentous reconstruction showing encouraging results with acceptable complications. Meccariello L, Caiaffa V, Mader K, et al. Treatment of Unstable Elbow Injuries with a Hinged Elbow Fixator: Subjective and Objective Results. Strategies Trauma Limb Reconstr 2022;17(2):68-73.


HLA class II alleles and risk for peripheral neuropathy in type 2 diabetes patients.
The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.


Zap1p, a metalloregulatory protein involved in zinc-responsive transcriptional regulation in Saccharomyces cerevisiae.
Zinc ion homeostasis in Saccharomyces cerevisiae is controlled primarily through the transcriptional regulation of zinc uptake systems in response to intracellular zinc levels. A high-affinity uptake system is encoded by the ZRT1 gene, and its expression is induced more than 30-fold in zinc-limited cells. A low-affinity transporter is encoded by the ZRT2 gene, and this system is also regulated by zinc. We used a genetic approach to isolate mutants whose ZRT1 expression is no longer repressed in zinc-replete cells, and a new gene, ZAP1, was identified. ZAP1 encodes a 93-kDa protein with sequence similarity to transcriptional activators; the C-terminal 174 amino acids contains five C2H2 zinc finger domains, and the N terminus (residues 1 to 706) has two potential acidic activation domains. The N-terminal region also contains 12% histidine and cysteine residues. The mutant allele isolated, ZAP1-1up, is semidominant and caused high-level expression of ZRT1 and ZRT2 in both zinc-limited and zinc-replete cells. This phenotype is the result of a mutation that substitutes a serine for a cysteine residue in the N-terminal region. A zap1 deletion mutant grew well on zinc-replete media but poorly on zinc-limiting media. This mutant had low-level ZRT1 and ZRT2 expression in zinc-limited as well as zinc-replete cells. These data indicate that Zap1p plays a central role in zinc ion homeostasis by regulating transcription of the zinc uptake system genes in response to zinc. Finally, we present evidence that Zap1p regulates transcription of its own promoter in response to zinc through a positive autoregulatory mechanism.


Report of Alliance of International Science Organizations on Disaster Risk Reduction (ANSO-DRR) Conference 2020.
This article summarizes the proceedings of the four-session meeting (webinar) conducted by the Alliance of International Science Organizations on Disaster Risk Reduction (ANSO-DRR) on 18 May 2020. ANSO-DRR is an international, nonprofit and nongovernmental scientific alliance bringing together academies of science, research organizations and universities which share a strong interest in disaster risk reduction in the regions along the land-based and maritime routes of the Belt and Road Initiative. ANSO-DRR convenes an annual meeting to review its work progress and discuss its scientific programs. The first session was the opening statements and was followed by the introduction and updates on ANSO-DRR in the second session. The third session was the depiction of the big picture of ANSO, the umbrella organization of ANSO-DRR, led by the Assistant Executive Director of ANSO, while the fourth session was a presentation of perspectives on the strategic development of ANSO-DRR. One of ANSO-DRR's key strategies is to enhance disaster mitigation and response through multidisciplinary cooperation among disaster and healthcare sciences (i.e., health emergency and disaster risk management (Health-EDRM)). It aims to enhance DRR efforts by performing as an instrument in connecting people along the Belt and Road regions, focusing on DRR resource and database development, involving higher education institutions in DRR efforts and increasing disaster resilience in built infrastructures.


Distinguishing PTSD, Complex PTSD, and Borderline Personality Disorder: A latent class analysis.
There has been debate regarding whether Complex Posttraumatic Stress Disorder (Complex PTSD) is distinct from Borderline Personality Disorder (BPD) when the latter is comorbid with PTSD. To determine whether the patterns of symptoms endorsed by women seeking treatment for childhood abuse form classes that are consistent with diagnostic criteria for PTSD, Complex PTSD, and BPD. A latent class analysis (LCA) was conducted on an archival dataset of 280 women with histories of childhood abuse assessed for enrollment in a clinical trial for PTSD. THE LCA REVEALED FOUR DISTINCT CLASSES OF INDIVIDUALS: a Low Symptom class characterized by low endorsements on all symptoms; a PTSD class characterized by elevated symptoms of PTSD but low endorsement of symptoms that define the Complex PTSD and BPD diagnoses; a Complex PTSD class characterized by elevated symptoms of PTSD and self-organization symptoms that defined the Complex PTSD diagnosis but low on the symptoms of BPD; and a BPD class characterized by symptoms of BPD. Four BPD symptoms were found to greatly increase the odds of being in the BPD compared to the Complex PTSD class: frantic efforts to avoid abandonment, unstable sense of self, unstable and intense interpersonal relationships, and impulsiveness. Findings supported the construct validity of Complex PTSD as distinguishable from BPD. Key symptoms that distinguished between the disorders were identified, which may aid in differential diagnosis and treatment planning.


Amiloride-sensitive trypsinization of apical sodium channels. Analysis of hormonal regulation of sodium transport in toad bladder.
Incubation of the mucosal surface of the toad urinary bladder with trypsin (1 mg/ml) irreversibly decreased the short-circuit current to 50% of the initial value. This decrease was accompanied by a proportionate decrease in apical Na permeability, estimated from the change in amiloride-sensitive resistance in depolarized preparations. In contrast, the paracellular resistance was unaffected by trypsinization. Amiloride, a specific blocker of the apical Na channels, prevented inactivation by trypsin. Inhibition of Na transport by substitution of mucosal Na, however, had no effect on the response to trypsin. Trypsinization of the apical membrane was also used to study regulation of Na transport by anti-diuretic hormone (ADH) and aldosterone. Prior exposure of the apical surface to trypsin did not reduce the response to ADH, which indicates that the ADH-induced Na channels were inaccessible to trypsin before addition of the hormone. On the other hand, stimulation of short-circuit current by aldosterone or pyruvate (added to substrate-depleted, aldosterone-repleted bladders) was substantially reduced by prior trypsinization of the apical surface. Thus, the increase in apical Na permeability elicited by aldosterone or substrate involves activation of Na channels that are continuously present in the apical membrane in nonconductive but trypsin-sensitive forms.


Toxicity of Polystyrene Nanoplastics in the Liver and Intestine of Normal and High-Fat-Diet Juvenile Zebrafish.
Nanoplastics (NPs) are widely found and threaten environmental and biological safety, because they do not degrade completely. We aimed to preliminarily explore the toxicity of NPs in obese children, because childhood obesity is a growing global health concern. We used zebrafish as a vertebrate toxicological model to examine the hepatic lipid metabolism and gut microbiota in juvenile zebrafish exposed to 1000 μg/L polystyrene NPs and a high-fat diet (HFD) using Raman spectroscopy, pathological examination, transcriptome analysis, and 16S sequencing techniques. Our study showed that polystyrene NPs perturb the lipid metabolism and gut microbiota stability in zebrafish. Furthermore, the combined effects of polystyrene NPs and HFD resulted in gastrointestinal injury. Our study is one of the first to investigate the toxicity of polystyrene NPs to normal-diet and HFD juvenile zebrafish using confocal Raman spectroscopy. Our results show the importance of a healthy diet and a reduction in the use of plasticware. Environ Toxicol Chem 2023;00:1-13. © 2023 SETAC.


Optimal Radiation Therapy for Small Cell Lung Cancer.
Radiation therapy plays an important role in the management of both limited stage and extensive stage small cell lung cancer. For limited stage disease, there has been a trend toward reduced size of thoracic radiation fields, which has the potential to reduce toxicity. FDG-PET staging helps make this possible by more accurately identifying areas of nodal and metastatic involvement. Trials have demonstrated similar outcomes using a range of radiation fractionation schedules, allowing flexibility in individualizing treatment. Using advanced radiation therapy techniques such as intensity-modulated radiation therapy, it may be possible to deliver fewer, higher dose fractions and achieve similar results to the hyperfractionated regimen. For extensive stage disease, consolidative thoracic radiation therapy after chemotherapy was recently shown to improve overall survival in certain patient subsets. Prophylactic cranial irradiation continues to play an important role in management of all stages of small cell lung cancer. Debate continues about the neurocognitive effects of this treatment, and whether MRI surveillance is an acceptable alternative. Strategies such as hippocampal avoidance may reduce the cognitive effects of prophylactic cranial irradiation in the future. Finally, in the last few years stereotactic ablative radiation therapy followed by chemotherapy has emerged as a promising treatment for stage I small cell lung cancer. This radiation treatment is usually given over 1-5 fractions and appears to provide a good rate of local control with a low rate of serious toxicity.


Venous thromboembolism hospitalizations among American Indians and Alaska Natives.
Cardiovascular disease (CVD) has been reported to be on the increase in the American Indian/Alaska Native (AI/AN) population. The Indian Health Service (IHS) hospital discharge database was used to describe venous thromboembolism (VTE)-associated hospitalizations among patients receiving IHS-reported medical care in the United States from 1980 through 1996. The average overall VTE-associated hospitalization rate in the AI/AN population during 1980-1996 was 33.1 per 100,000, however, the rate significantly decreased from 38.4 per 100,000 AI/ANs in 1980-1982 to 33.2 in 1994-1996. The average age at hospitalization was 50.4 years, which was consistent during the 17-year period. The overall annual VTE hospitalization rate was higher for females than for males (38.0 versus 27.7 per 100,000). The female VTE hospitalization rates decreased significantly from 46.1 per 100,000 in 1980-1982 to 36.7 per 100,000 in 1994-1996 (risk ratio: RR=1.3; 95% confidence interval: CI=1.1-1.4), while the rates for males remained unchanged. The VTE hospitalization rates also varied by geographic region. The hospitalization rate was highest in the East region (52.2 per 100,000) and lowest in the Alaska region (16.1 per 100,000). These data indicate that the overall VTE rate for AI/ANs may not have only decreased, but appears lower than the reported rate for Caucasians.


Dedicated training in adult education among otolaryngology faculty.
Most faculty members undergo ad hoc training in education. This survey was developed to assess the prevalence and type of dedicated training in education received by academic otolaryngology-head and neck surgery (OTO-HNS) faculty in the United States. Survey. An 11-item survey was developed to assess the prevalence of dedicated instruction in education theory and practice, the types of instruction received, and the barriers to receiving instruction. The survey was sent to all OTO-HNS program directors for distribution among their respective faculty. A total of 216 responses were received. Seventy respondents (32.7%) serve as program director, associate program director, or assistant program director in their respective programs. Forty-six respondents (21.8%) had received dedicated training in education. Of the respondents who described the type of education training received, 48.7% participated in didactics/seminar, 35.9% in degree/certificate programs, 10.3% in multimodality training, and 5.1% online training. Among the barriers encountered to participation in instruction in education, time/productivity pressures was the most commonly cited reason (60.2%), followed by not knowing about the opportunity to receive training (36.4%), lack of departmental support (26.2%), lack of available training (22.3%), and the perception that such training would not be useful (7.8%). Presently, only a minority of surveyed academic otolaryngologists in the United States have received any dedicated instruction in the theory and practice of education. Personal, departmental, and institutional barriers exist in many practice environments that hinder otolaryngology faculty from participating in education training. N/A.